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Clinical Study to Compare the Efficacy and Safety of Macitentan and Tadalafil Monotherapies With the Corresponding Fixed-dose Combination Therapy in Subjects With Pulmonary Arterial Hypertension (PAH) (A DUE)

Primary Purpose

Pulmonary Arterial Hypertension (PAH) (WHO Group 1 PH)

Status
Active
Phase
Phase 3
Locations
International
Study Type
Interventional
Intervention
FDC macitentan/tadalafil
Macitentan 10 mg
Tadalafil 40 mg
Placebo FDC
Placebo macitentan
Placebo tadalafil
Sponsored by
Actelion
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Pulmonary Arterial Hypertension (PAH) (WHO Group 1 PH) focused on measuring Pulmonary Arterial Hypertension, PAH, macitentan, tadalafil, fixed dose combination therapy

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

  • Signed and dated informed consent form (ICF)
  • Confirmed diagnosis of symptomatic PAH in WHO FC II or III
  • Symptomatic PAH belonging to one of the following subgroups of WHO Group 1 pulmonary hypertension:

    • Idiopathic
    • Heritable
    • Drug- or toxin-induced
    • Associated with connective tissue disease, HIV infection, portal hypertension or congenital heart disease with simple systemic-to-pulmonary shunt with persistent pulmonary hypertension documented by a right heart catheterization (RHC) ≥ 1 year after surgical repair
  • PAH diagnosis confirmed by hemodynamic evaluation at rest (through central reading), evaluated within 5 weeks prior to randomization:

    • Mean pulmonary artery pressure (mPAP) ≥ 25 mmHg, AND
    • Pulmonary artery wedge pressure (PAWP) or left ventricular end diastolic pressure (LVEDP) ≤ 15 mmHg, AND
    • Pulmonary vascular resistance (PVR) ≥ 3 WU (i.e., ≥ 240 dyn∙sec∙cm-5)
  • Negative vasoreactivity test in idiopathic, heritable, and drug/toxin-induced PAH. (Participants for whom no vasoreactivity test was performed at diagnosis can be eligible if currently treated with PAH therapy for more than 3 months and PAH diagnosis confirmed by hemodynamic evaluation at least 3 months after introduction of their PAH therapy).
  • Currently receiving a stable dose of ERA or PDE-5i monotherapy for at least 3 months prior to baseline RHC, within the prespecified doses in the study protocol or no history of PAH-specific treatment
  • Participant able to perform the 6MWT with a minimum distance of 100 m and maximum distance of 450 m at Screening
  • A woman of childbearing potential must:

    • have negative serum pregnancy test at Screening and a negative urine pregnancy test at Randomization
    • agree to undertake monthly urine pregnancy tests during the study and up to at least 30 days after study treatment discontinuation
    • agree to follow the contraception scheme from Screening up to at least 30 days after study treatment discontinuation

Exclusion Criteria:

  • Treatment with a soluble guanylate cyclase stimulator, L-arginine, any form of prostanoids or prostacyclin-receptor agonists (including oral, inhaled, or infused routes) in the 3-month period prior to start of treatment
  • Treatment with combination therapy of ERA and PDE-5i in the 3-month period prior to start of treatment or history of intolerance to ERA and PDE-5i combination therapy
  • Hypersensitivity to any of the study treatments or any excipient of their formulations
  • Treatment with a strong cytochrome P450 3A4 (CYP3A4) inducer in the 1-month period prior to start of treatment
  • Treatment with a strong CYP3A4 inhibitor or a moderate dual CYP3A4/CYP2C9 inhibitor or co-administration of a combination of moderate CYP3A4 and moderate CYP2C9 inhibitors in the 1-month period prior to start of treatment
  • Treatment with doxazosin
  • Treatment with any form of organic nitrate, either regularly or intermittently
  • Diuretic treatment initiated or dose changed within 1 week prior to the RHC or start of treatment
  • Treatment with another investigational drug in the 3-month period prior to start of treatment
  • Body mass index (BMI) > 40 kg/m2 at Screening
  • Known presence of three or more of the following risk factors for heart failure with preserved ejection fraction at Screening:

    • BMI > 30 kg/m2
    • Diabetes mellitus of any type
    • Essential hypertension (even if well controlled)
    • Coronary artery disease, i.e. history of stable angina or known more than 50% stenosis in a coronary artery or history of myocardial infarction or history of or planned coronary artery bypass grafting and/or coronary artery stenting
  • Known presence of moderate or severe obstructive lung disease any time prior to Screening as specified in study protocol
  • Known presence of moderate or severe restrictive lung disease any time prior to Screening as specified in study protocol
  • Clinically significant aortic or mitral valve disease; pericardial constriction; restrictive or congestive left-sided cardiomyopathy; life-threatening cardiac arrhythmias; significant left ventricular dysfunction; or left ventricular outflow obstruction, in the opinion of the investigator
  • Known permanent atrial fibrillation, in the opinion of the investigator
  • Known or suspected uncontrolled thyroid disease (hypo- or hyperthyroidism)
  • Documented pulmonary veno-occlusive disease
  • Hemoglobin < 100 g/L (<10 g/dL) at Screening
  • Known severe hepatic impairment as specified in study protocol
  • Serum aspartate aminotransferase (AST) and/or alanine aminotransferase (ALT) > 1.5 × upper limit of normal (ULN) at Screening
  • Severe renal impairment at Screening as specified in study protocol
  • Systemic hypotension at Screening or Randomization and systemic hypertension at Screening as specified in study protocol
  • Acute myocardial infarction or cerebrovascular event (e.g., stroke) within the last 26 weeks prior to Screening
  • Known bleeding disorder, in the opinion of the investigator
  • Loss of vision in one or both eyes because of non-arteritic anterior ischemic optic neuropathy
  • Hereditary degenerative retinal disorders, including retinitis pigmentosa
  • History of priapism, conditions that predispose to priapism (example, sickle cell anemia, multiple myeloma, or leukemia) or anatomical deformation of the penis (example, angulation, cavernosal fibrosis, or Peyronie's disease)
  • Difficulty swallowing large pills/tablets that would interfere with the ability to comply with study treatment regimen
  • Any planned surgical intervention (including organ transplant) during the double-blind treatment period, except minor interventions
  • Exercise training program for cardiopulmonary rehabilitation in the 12-week period prior to start of treatment, or planned to be started during the double-blind period of the study
  • Pregnant, planning to become pregnant or lactating
  • Any known factor or disease that might interfere with treatment adherence, full participation in the study or interpretation of the results as judged by the investigator (e.g., drug or alcohol dependence etc.)
  • Known concomitant life-threatening disease with a life expectancy less than (<) 12 months
  • Calcium channel blocker treatment initiated, or dose changed within 3 months prior to right heart catheterization (RHC) at screening

Sites / Locations

  • St. Joseph Hearitage Healthcare
  • University of Southern California
  • Piedmont Healthcare
  • WellStar Health System
  • OSF HealthCare Cardiovascular Institute
  • University of Iowa Hospitals & Clinics
  • Norton Healthcare
  • Sparrow Clinical Research Institute
  • Minneapolis Heart Institute Foundation
  • Washington University School of Medicine
  • VA Sierra Nevada Health Care System
  • The University of North Carolina at Chapel Hill
  • Pitt County Memorial Hospital d/b/a Vidant Medical Center
  • Sanford Health
  • University of Cincinnati
  • St. Elizabeth Hospital Mercy Bon Secors
  • Legacy Hospital
  • Oregon Health and Science University
  • Thomas Jefferson University Hospital
  • University of Pittsburgh Medical Center
  • Sanford Health
  • University of Texas Southwestern Medical Center
  • Baylor Scott White - Plano
  • WVU Health Sciences Center
  • University of Wisconsin At Madison
  • Medical College of Wisconsin-Froedtert Hospital
  • Royal Adelaide Hospital
  • Pulmonary Arterial Hypertension Clinic
  • Core Research Group
  • Universidade Federal De Minas Gerais - Hospital das Clínicas
  • Instituto das Pequenas Missionárias de Maria Imaculada - Hospital Madre Teresa
  • Fundacao para o Desenvolvimento Medico Hospitalar (UNESP Botucatu)
  • Secretaria da Saude do Estado do Ceara - Hospital Doutor Carlos Alberto Studart Gomes
  • Universidade Federal de Goias - Hospital das Clinicas da UFG
  • Hospital das Clinicas de Porto Alegre
  • Irmandade Santa Casa de Misericordia de Porto Alegre
  • União Brasileira de Educação e Assistência-Hospital São Lucas da PUCRS
  • Hospital Das Clinicas Da Faculdade De Medicina Da USP
  • SPDM - Associacao Paulista para o Desenvolvimento da Medicina - Hospital Sao Paulo
  • National Heart Hospital
  • University Multiprofile Hospital for Active Treatment- UMHAT Sveta Anna AD
  • Alberta Health Services
  • University of Alberta
  • Vancouver General Hospital
  • London Health Sciences Centre
  • Beijing Anzhen Hospital
  • The Second Xiangya Hospital of Central South Hospital
  • The First Affiliated Hospital of Guangzhou Medical University
  • Jiangsu Province Hospital
  • Shanghai Pulmonary Hospital
  • The General Hospital of Northern Theater Command
  • Tianjin Medical University General Hospital
  • The First Affiliated Hospital of Xi'an Jiaotong University
  • General University Hospital II.department of Internal Medicine-cardiology and angiology
  • Universitatsklinikum Bonn
  • Universitätsklinikum Carl Gustav Carus Dresden
  • Universitaetsklinikum Giessen
  • Universitat Greifswald
  • Universitaetsklinikum Hamburg Eppendorf
  • Thoraxklinik am Universitätsklinikum Heidelberg
  • Kardiologische Praxis Papenburg
  • Universitaetsklinikum Regensburg
  • Klinikum Würzburg Mitte gGmbH Standort Missioklinik
  • Semmelweis Egyetem,Pulmonológiai Klinika
  • Gottsegen György Országos Kardiológiai Intézet, Felnőtt kardiológiai osztály
  • Pecsi Tudomanyegyetem Klinikai Kozpont
  • Szegedi Tudomanyegyetem
  • Azienda Ospedaliero Universitaria Consorziale Policlinico di Bari
  • Cardiologia c/o Spedali Civili
  • Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico
  • Azienda Ospedaliera San Gerardo
  • Ospedale San Francesco
  • IRCCS Policlinico San Matteo, Università degli studi di Pavi
  • Policlinico Umberto I
  • The University of Tokyo Hospital
  • Chiba University Hospital
  • Kyushu University Hospital
  • Fukushima Medical University Hospital
  • Gunma University Hospital
  • Kure Kyosai Hospital
  • Tokai University Hospital
  • Kagoshima University Hospital
  • Kanazawa University Hospital
  • Kobe University Hospital
  • Kumamoto University Hospital
  • Kurume University Hospital
  • University Hospital Kyoto Perfectural University of Medicine
  • Kyoto University Hospital
  • Shinshu University Hospital
  • Kyorin University Hospital
  • Nagasaki University Hospital
  • Okayama University Hospital
  • National Hospital Organization Okayama Medical Center
  • Hokkaido University Hospital
  • Sapporo Medical University Hospital
  • Tohoku University Hospital
  • National Cerebral and Cardiovascular Center
  • Juntendo University Hospital
  • University of Tsukuba Hospital
  • Mie University Hospital
  • Institut Jantung Negara (National Heart Institute)
  • Sarawak Heart Center
  • Instituto Nacional de Cardiologia Dr. Ignacio Chavez
  • Unidad de Investigacion Clinica en Medicina S.C. (UDICEM)
  • Klinika Kardiologii z Oddzialem Intensywnego Nadzoru Kardiologicznego, UM w Białymstoku
  • Szpital Uniwersytecki nr 2 im dr Jana Biziela w Bydgoszczy, Klinika Kardiologii
  • Uniwersyteckie Centrum Kliniczne
  • GCM SUM, I Oddzial Kardiologii
  • Oddzial Kardiologii Wojewodzki Szpital Specjalistyczny im. W.Bieganskiego
  • Wojewodzki Szpital Specjalistyczny im. Stefana Kardynala Wyszynskiego SPZOZ, Oddzial Kardiologii
  • ECZ Otwock Klinika Kardiologii, Klinika Krążenia Płucnego Chorób Zakrzepowo-Zatorowych i Kardiologii
  • SPSK2 PUM, Klinika Kardiologii
  • Wojewodzki Szpital Specjalistyczny, Oddzial Kardiologiczny
  • Altay Regional Cardiological Dispensary
  • Scientific and Research Institution of Cardiovascular Diseases Complex Problems
  • National Medical Research Center of Cardiology of MoH of Russian Federation
  • GU Moscow Regional Research Clinical Institute n.a. M.F.Vla
  • National medical Research Center n.a. V.A.Almazov of MoH of Russian Federation
  • Samara Regional Clinical Cardiological Dispensary
  • Abdullah, IA
  • Dr Kalla
  • Hosp. Clinic I Provincial de Barcelona
  • Hosp. Univ. Vall D Hebron
  • Hosp. Univ. Ramon Y Cajal
  • Hosp. Univ. Fund. Jimenez Diaz
  • Hosp. Univ. La Paz
  • Hosp. Clinico Univ. de Salamanca
  • Hosp. Univ. Marques de Valdecilla
  • Hosp. Virgen de La Salud
  • Hosp. Gral. Univ. Valencia
  • Kaohsiung Veterans General Hospital
  • National Cheng Kung University Hospital
  • National Taiwan University Hospital
  • Mackay Memorial Hospital
  • Taipei Veterans General Hospital
  • Chang-Gung Memorial Hospital, LinKou Branch
  • Cukurova University Medical Faculty
  • Hacettepe University Medical Faculty
  • Ankara University Medical Faculty
  • Bursa Yuksek Ihtisas Training and Research Hospital
  • Istanbul University - Cerrahpasa Cardiology Institution
  • Istanbul University Cerrahpasa Medical Faculty
  • Marmara University Medical Faculty
  • Ege University School of Medicine
  • Dokuz Eylul University Hospital
  • Kartal Kosuyolu Yuksek Ihtisas Egitim Ve Arastirma Hastanesi
  • Konya Selcuk University Medical Faculty
  • Mersin University Medical Faculty

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm Type

Experimental

Active Comparator

Active Comparator

Arm Label

FDC therapy + Placebo macitentan + Placebo tadalafil

Macitentan mono-therapy + Placebo tadalafil + Placebo FDC

Tadalafil mono-therapy + Placebo macitentan + Placebo FDC

Arm Description

Subjects to receive FDC macitentan/tadalafil (macitentan 10 mg and tadalafil 40 mg) plus matching placebos for the two other study treatments.

Subjects to receive macitentan 10 mg plus matching placebos for the two other study treatments.

Subjects to receive tadalafil 40 mg (2 x 20 mg) plus matching placebos for the two other study treatments.

Outcomes

Primary Outcome Measures

Change in Pulmonary Vascular Resistance (PVR) expressed as the ratio of geometric means of End of Double-Blind Treatment (EDBT) to baseline
PVR is the resistance in the pulmonary vasculature that has to be overcome to push blood from the right side of the heart to the lungs. PVR measured by Right Heart Catheterization (RHC) has diagnostic and prognostic value as well as offers an objective judgement on treatment response and efficacy.

Secondary Outcome Measures

Change in 6-minute walk distance (6MWD) from baseline to EDBT
The purpose of the six-minute walk test (6MWT) is to quantify exercise tolerance and capacity. This standardized test measures the distance an individual is able to walk over a total of six minutes on a hard, flat surface. The goal is for the individual to walk as far as possible in six minutes. This endpoint is associated with prognosis and clinical outcomes such as improvement of hemodynamics.
Change From Baseline in Cardiopulmonary Symptom Domain Score in PAH-SYMPACT to Week 16
Pulmonary Arterial Hypertension-Symptoms and Impact (PAH-SYMPACT) is a PAH-specific patient-reported outcomes instrument that quantifies PAH symptoms and impacts. The Symptom part is a daily diary that contains 11 items. The respondent is asked to rate each of the items for the past 24 hours. The response options for each item range from 0 " "no [symptom] at all" to 4 "very severe".
Change From Baseline in Cardiovascular Symptom Domain Score in PAH-SYMPACT to Week 16
PAH-SYMPACT is a PAH-specific patient-reported outcomes instrument that quantifies PAH symptoms and impacts. The Symptom part is a daily diary that contains 11 items. The respondent is asked to rate each of the items for the past 24 hours. The response options for each item range from 0 " "no [symptom] at all" to 4 "very severe".
Proportion of subjects with absence of worsening in World Health Organization (WHO) Functional Class (FC) from baseline to EDBT.
WHO FC reflects the severity of a PAH patient's symptoms and the impact of these symptoms on their activities of daily life. WHO FC is directly associated with prognosis and improvement in WHO FC correlates with survival in subjects with PAH.

Full Information

First Posted
April 4, 2019
Last Updated
September 12, 2023
Sponsor
Actelion
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1. Study Identification

Unique Protocol Identification Number
NCT03904693
Brief Title
Clinical Study to Compare the Efficacy and Safety of Macitentan and Tadalafil Monotherapies With the Corresponding Fixed-dose Combination Therapy in Subjects With Pulmonary Arterial Hypertension (PAH)
Acronym
A DUE
Official Title
Prospective, Multi-center, Double-blind, Randomized, Active-controlled, Triple-dummy, Parallel-group, Group-sequential, Adaptive Phase 3 Clinical Study to Compare the Efficacy and Safety of Macitentan and Tadalafil Monotherapies With the Corresponding Fixed Dose Combination in Subjects With Pulmonary Arterial Hypertension (PAH), Followed by an Open-label Treatment Period With Macitentan and Tadalafil Fixed Dose Combination Therapy
Study Type
Interventional

2. Study Status

Record Verification Date
September 2023
Overall Recruitment Status
Active, not recruiting
Study Start Date
July 29, 2019 (Actual)
Primary Completion Date
August 23, 2022 (Actual)
Study Completion Date
September 24, 2024 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Actelion

4. Oversight

Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes

5. Study Description

Brief Summary
Combination therapy in pulmonary arterial hypertension (PAH) has been the subject of active investigation for more than a decade, with the benefit of targeting different pathways known to be involved in the pathogenesis of the disease. Adherence to prescribed therapy has an impact on clinical outcomes. Reducing the pill/tablet count and frequency has a major impact on patients' adherence to therapies and therefore the observed clinical outcomes. One way to simplify treatment is to use fixed-dose combination (FDC) products that combine multiple treatments targeting different pathways into a single tablet. This study aims to demonstrate that the FDC of macitentan and tadalafil is more effective than therapy with 10 mg of macitentan alone or 40 mg of tadalafil alone. This phase 3 study will evaluate the efficacy and safety at 16 weeks of an FDC (macitentan 10 mg and tadalafil 40 mg) against these two PAH-approved therapies given as monotherapy to further confirm the added value of the FDC.
Detailed Description
PAH is characterized by a progressive increase in pulmonary arterial pressure (PAP) and in pulmonary vascular resistance (PVR) potentially leading to right heart failure and death. Current PAH-specific therapeutic options include treatments that target the three pathways (endothelin, nitric oxide, and prostacyclin pathways). While combination treatment is common, FDC pills or tablets that combine two or more PAH-specific therapies are not available, thereby requiring participants to take multiple pills/tablets daily. An FDC is an attractive option for PAH participants because it simplifies the treatment regimen by combining two therapies (which would otherwise involve a total of three tablets: one macitentan 10 mg tablet and two tadalafil 20 mg tablets) into a single tablet. Macitentan is an orally active, non-peptide, potent dual endothelin receptor A and B antagonist. Tadalafil is a selective inhibitor of phosphodiesterase type-5 (PDE-5), the enzyme responsible for the degradation of cyclic guanosine monophosphate (cGMP). This study comprises the following consecutive periods: Screening period (lasts up to 30 days), Double-blind treatment period (consists of the titration phase [the first 2 weeks] and the maintenance phase [Week 3 through Week 16]), Open-label treatment period, End-of-Treatment (EOT), Safety follow-up (S-FU) period, and End of Study (EOS). The total study duration for a participant will be up to 30 months. Study assessments like physical examinations, vital signs, right heart catheterization, 6-minute walk test will be performed. Safety will be assessed throughout the study.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Pulmonary Arterial Hypertension (PAH) (WHO Group 1 PH)
Keywords
Pulmonary Arterial Hypertension, PAH, macitentan, tadalafil, fixed dose combination therapy

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 3
Interventional Study Model
Parallel Assignment
Model Description
In total, approximately 170 subjects are planned to be randomized into study to receive either FDC macitentan/tadalafil or macitentan 10 mg or tadalafil 40 mg given once daily and will also receive matching placebos for two other study treatments. Treatment allocation will be stratified based on prior PAH therapy (i.e., treatment-naïve or treated by an Endothelin receptor antagonist or a Phosphodiesterase type-5 inhibitor as a monotherapy) at baseline. Sample size will be re-estimated at interim analysis if study is not terminated early for efficacy/futility up to sample size of 150-250. After completion of double-blind treatment period, subjects will continue study in an open-label treatment (OLT) period for 24 months, which may be prolonged beyond 24 months until macitentan and tadalafil are accessible at required doses, through other options according to local regulations. All assessments at end of double-blind treatment must be completed before subject enters OLT period.
Masking
ParticipantCare ProviderInvestigatorOutcomes Assessor
Allocation
Randomized
Enrollment
187 (Actual)

8. Arms, Groups, and Interventions

Arm Title
FDC therapy + Placebo macitentan + Placebo tadalafil
Arm Type
Experimental
Arm Description
Subjects to receive FDC macitentan/tadalafil (macitentan 10 mg and tadalafil 40 mg) plus matching placebos for the two other study treatments.
Arm Title
Macitentan mono-therapy + Placebo tadalafil + Placebo FDC
Arm Type
Active Comparator
Arm Description
Subjects to receive macitentan 10 mg plus matching placebos for the two other study treatments.
Arm Title
Tadalafil mono-therapy + Placebo macitentan + Placebo FDC
Arm Type
Active Comparator
Arm Description
Subjects to receive tadalafil 40 mg (2 x 20 mg) plus matching placebos for the two other study treatments.
Intervention Type
Drug
Intervention Name(s)
FDC macitentan/tadalafil
Other Intervention Name(s)
ACT-064992D
Intervention Description
Film-coated tablet with 10 mg macitentan and 40 mg tadalafil, to be administered orally once daily.
Intervention Type
Drug
Intervention Name(s)
Macitentan 10 mg
Other Intervention Name(s)
ACT-064992
Intervention Description
Film-coated tablet with 10 mg macitentan, to be administered orally once daily.
Intervention Type
Drug
Intervention Name(s)
Tadalafil 40 mg
Intervention Description
Film-coated tablet with 40 mg tadalafil (2 x 20 mg tablets), to be administered orally once daily.
Intervention Type
Drug
Intervention Name(s)
Placebo FDC
Intervention Description
Matching placebo not containing any active substance but otherwise identical in appearance to the respective active drug tablet, to be administered orally once daily.
Intervention Type
Drug
Intervention Name(s)
Placebo macitentan
Intervention Description
Matching placebo not containing any active substance but otherwise identical in appearance to the respective active drug tablet, to be administered orally once daily.
Intervention Type
Drug
Intervention Name(s)
Placebo tadalafil
Intervention Description
Matching placebo not containing any active substance but otherwise identical in appearance to the respective active drug tablet, to be administered orally once daily.
Primary Outcome Measure Information:
Title
Change in Pulmonary Vascular Resistance (PVR) expressed as the ratio of geometric means of End of Double-Blind Treatment (EDBT) to baseline
Description
PVR is the resistance in the pulmonary vasculature that has to be overcome to push blood from the right side of the heart to the lungs. PVR measured by Right Heart Catheterization (RHC) has diagnostic and prognostic value as well as offers an objective judgement on treatment response and efficacy.
Time Frame
From baseline to EDBT (Week 16)
Secondary Outcome Measure Information:
Title
Change in 6-minute walk distance (6MWD) from baseline to EDBT
Description
The purpose of the six-minute walk test (6MWT) is to quantify exercise tolerance and capacity. This standardized test measures the distance an individual is able to walk over a total of six minutes on a hard, flat surface. The goal is for the individual to walk as far as possible in six minutes. This endpoint is associated with prognosis and clinical outcomes such as improvement of hemodynamics.
Time Frame
From baseline to EDBT (Week 16)
Title
Change From Baseline in Cardiopulmonary Symptom Domain Score in PAH-SYMPACT to Week 16
Description
Pulmonary Arterial Hypertension-Symptoms and Impact (PAH-SYMPACT) is a PAH-specific patient-reported outcomes instrument that quantifies PAH symptoms and impacts. The Symptom part is a daily diary that contains 11 items. The respondent is asked to rate each of the items for the past 24 hours. The response options for each item range from 0 " "no [symptom] at all" to 4 "very severe".
Time Frame
From Baseline to Week 16
Title
Change From Baseline in Cardiovascular Symptom Domain Score in PAH-SYMPACT to Week 16
Description
PAH-SYMPACT is a PAH-specific patient-reported outcomes instrument that quantifies PAH symptoms and impacts. The Symptom part is a daily diary that contains 11 items. The respondent is asked to rate each of the items for the past 24 hours. The response options for each item range from 0 " "no [symptom] at all" to 4 "very severe".
Time Frame
From Baseline to Week 16
Title
Proportion of subjects with absence of worsening in World Health Organization (WHO) Functional Class (FC) from baseline to EDBT.
Description
WHO FC reflects the severity of a PAH patient's symptoms and the impact of these symptoms on their activities of daily life. WHO FC is directly associated with prognosis and improvement in WHO FC correlates with survival in subjects with PAH.
Time Frame
From baseline to EDBT (Week 16)

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: Signed and dated informed consent form (ICF) Confirmed diagnosis of symptomatic PAH in WHO FC II or III Symptomatic PAH belonging to one of the following subgroups of WHO Group 1 pulmonary hypertension: Idiopathic Heritable Drug- or toxin-induced Associated with connective tissue disease, HIV infection, portal hypertension or congenital heart disease with simple systemic-to-pulmonary shunt with persistent pulmonary hypertension documented by a right heart catheterization (RHC) ≥ 1 year after surgical repair PAH diagnosis confirmed by hemodynamic evaluation at rest (through central reading), evaluated within 5 weeks prior to randomization: Mean pulmonary artery pressure (mPAP) ≥ 25 mmHg, AND Pulmonary artery wedge pressure (PAWP) or left ventricular end diastolic pressure (LVEDP) ≤ 15 mmHg, AND Pulmonary vascular resistance (PVR) ≥ 3 WU (i.e., ≥ 240 dyn∙sec∙cm-5) Negative vasoreactivity test in idiopathic, heritable, and drug/toxin-induced PAH. (Participants for whom no vasoreactivity test was performed at diagnosis can be eligible if currently treated with PAH therapy for more than 3 months and PAH diagnosis confirmed by hemodynamic evaluation at least 3 months after introduction of their PAH therapy). Currently receiving a stable dose of ERA or PDE-5i monotherapy for at least 3 months prior to baseline RHC, within the prespecified doses in the study protocol or no history of PAH-specific treatment Participant able to perform the 6MWT with a minimum distance of 100 m and maximum distance of 450 m at Screening A woman of childbearing potential must: have negative serum pregnancy test at Screening and a negative urine pregnancy test at Randomization agree to undertake monthly urine pregnancy tests during the study and up to at least 30 days after study treatment discontinuation agree to follow the contraception scheme from Screening up to at least 30 days after study treatment discontinuation Exclusion Criteria: Treatment with a soluble guanylate cyclase stimulator, L-arginine, any form of prostanoids or prostacyclin-receptor agonists (including oral, inhaled, or infused routes) in the 3-month period prior to start of treatment Treatment with combination therapy of ERA and PDE-5i in the 3-month period prior to start of treatment or history of intolerance to ERA and PDE-5i combination therapy Hypersensitivity to any of the study treatments or any excipient of their formulations Treatment with a strong cytochrome P450 3A4 (CYP3A4) inducer in the 1-month period prior to start of treatment Treatment with a strong CYP3A4 inhibitor or a moderate dual CYP3A4/CYP2C9 inhibitor or co-administration of a combination of moderate CYP3A4 and moderate CYP2C9 inhibitors in the 1-month period prior to start of treatment Treatment with doxazosin Treatment with any form of organic nitrate, either regularly or intermittently Diuretic treatment initiated or dose changed within 1 week prior to the RHC or start of treatment Treatment with another investigational drug in the 3-month period prior to start of treatment Body mass index (BMI) > 40 kg/m2 at Screening Known presence of three or more of the following risk factors for heart failure with preserved ejection fraction at Screening: BMI > 30 kg/m2 Diabetes mellitus of any type Essential hypertension (even if well controlled) Coronary artery disease, i.e. history of stable angina or known more than 50% stenosis in a coronary artery or history of myocardial infarction or history of or planned coronary artery bypass grafting and/or coronary artery stenting Known presence of moderate or severe obstructive lung disease any time prior to Screening as specified in study protocol Known presence of moderate or severe restrictive lung disease any time prior to Screening as specified in study protocol Clinically significant aortic or mitral valve disease; pericardial constriction; restrictive or congestive left-sided cardiomyopathy; life-threatening cardiac arrhythmias; significant left ventricular dysfunction; or left ventricular outflow obstruction, in the opinion of the investigator Known permanent atrial fibrillation, in the opinion of the investigator Known or suspected uncontrolled thyroid disease (hypo- or hyperthyroidism) Documented pulmonary veno-occlusive disease Hemoglobin < 100 g/L (<10 g/dL) at Screening Known severe hepatic impairment as specified in study protocol Serum aspartate aminotransferase (AST) and/or alanine aminotransferase (ALT) > 1.5 × upper limit of normal (ULN) at Screening Severe renal impairment at Screening as specified in study protocol Systemic hypotension at Screening or Randomization and systemic hypertension at Screening as specified in study protocol Acute myocardial infarction or cerebrovascular event (e.g., stroke) within the last 26 weeks prior to Screening Known bleeding disorder, in the opinion of the investigator Loss of vision in one or both eyes because of non-arteritic anterior ischemic optic neuropathy Hereditary degenerative retinal disorders, including retinitis pigmentosa History of priapism, conditions that predispose to priapism (example, sickle cell anemia, multiple myeloma, or leukemia) or anatomical deformation of the penis (example, angulation, cavernosal fibrosis, or Peyronie's disease) Difficulty swallowing large pills/tablets that would interfere with the ability to comply with study treatment regimen Any planned surgical intervention (including organ transplant) during the double-blind treatment period, except minor interventions Exercise training program for cardiopulmonary rehabilitation in the 12-week period prior to start of treatment, or planned to be started during the double-blind period of the study Pregnant, planning to become pregnant or lactating Any known factor or disease that might interfere with treatment adherence, full participation in the study or interpretation of the results as judged by the investigator (e.g., drug or alcohol dependence etc.) Known concomitant life-threatening disease with a life expectancy less than (<) 12 months Calcium channel blocker treatment initiated, or dose changed within 3 months prior to right heart catheterization (RHC) at screening
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Hany Rofael, MD
Organizational Affiliation
Janssen, LP
Official's Role
Study Director
Facility Information:
Facility Name
St. Joseph Hearitage Healthcare
City
Fullerton
State/Province
California
ZIP/Postal Code
92835
Country
United States
Facility Name
University of Southern California
City
Los Angeles
State/Province
California
ZIP/Postal Code
90033
Country
United States
Facility Name
Piedmont Healthcare
City
Atlanta
State/Province
Georgia
ZIP/Postal Code
30309
Country
United States
Facility Name
WellStar Health System
City
Marietta
State/Province
Georgia
ZIP/Postal Code
30060
Country
United States
Facility Name
OSF HealthCare Cardiovascular Institute
City
Peoria
State/Province
Illinois
ZIP/Postal Code
61614
Country
United States
Facility Name
University of Iowa Hospitals & Clinics
City
Iowa City
State/Province
Iowa
ZIP/Postal Code
52242
Country
United States
Facility Name
Norton Healthcare
City
Louisville
State/Province
Kentucky
ZIP/Postal Code
40202-1332
Country
United States
Facility Name
Sparrow Clinical Research Institute
City
Lansing
State/Province
Michigan
ZIP/Postal Code
48912
Country
United States
Facility Name
Minneapolis Heart Institute Foundation
City
Minneapolis
State/Province
Minnesota
ZIP/Postal Code
55407
Country
United States
Facility Name
Washington University School of Medicine
City
Saint Louis
State/Province
Missouri
ZIP/Postal Code
63110
Country
United States
Facility Name
VA Sierra Nevada Health Care System
City
Reno
State/Province
Nevada
ZIP/Postal Code
89509
Country
United States
Facility Name
The University of North Carolina at Chapel Hill
City
Chapel Hill
State/Province
North Carolina
ZIP/Postal Code
27514
Country
United States
Facility Name
Pitt County Memorial Hospital d/b/a Vidant Medical Center
City
Greenville
State/Province
North Carolina
ZIP/Postal Code
27835
Country
United States
Facility Name
Sanford Health
City
Fargo
State/Province
North Dakota
ZIP/Postal Code
58122
Country
United States
Facility Name
University of Cincinnati
City
Cincinnati
State/Province
Ohio
ZIP/Postal Code
45267
Country
United States
Facility Name
St. Elizabeth Hospital Mercy Bon Secors
City
Youngstown
State/Province
Ohio
ZIP/Postal Code
44503
Country
United States
Facility Name
Legacy Hospital
City
Portland
State/Province
Oregon
ZIP/Postal Code
97210
Country
United States
Facility Name
Oregon Health and Science University
City
Portland
State/Province
Oregon
ZIP/Postal Code
97239
Country
United States
Facility Name
Thomas Jefferson University Hospital
City
Philadelphia
State/Province
Pennsylvania
ZIP/Postal Code
19107
Country
United States
Facility Name
University of Pittsburgh Medical Center
City
Pittsburgh
State/Province
Pennsylvania
ZIP/Postal Code
15213
Country
United States
Facility Name
Sanford Health
City
Sioux Falls
State/Province
South Dakota
ZIP/Postal Code
57105
Country
United States
Facility Name
University of Texas Southwestern Medical Center
City
Dallas
State/Province
Texas
ZIP/Postal Code
75390
Country
United States
Facility Name
Baylor Scott White - Plano
City
Plano
State/Province
Texas
ZIP/Postal Code
75093
Country
United States
Facility Name
WVU Health Sciences Center
City
Morgantown
State/Province
West Virginia
ZIP/Postal Code
26506
Country
United States
Facility Name
University of Wisconsin At Madison
City
Madison
State/Province
Wisconsin
ZIP/Postal Code
53792
Country
United States
Facility Name
Medical College of Wisconsin-Froedtert Hospital
City
Milwaukee
State/Province
Wisconsin
ZIP/Postal Code
53226
Country
United States
Facility Name
Royal Adelaide Hospital
City
Adelaide
ZIP/Postal Code
5000
Country
Australia
Facility Name
Pulmonary Arterial Hypertension Clinic
City
Hobart
ZIP/Postal Code
7000
Country
Australia
Facility Name
Core Research Group
City
Milton
ZIP/Postal Code
4064
Country
Australia
Facility Name
Universidade Federal De Minas Gerais - Hospital das Clínicas
City
Belo Horizonte
ZIP/Postal Code
30130-100
Country
Brazil
Facility Name
Instituto das Pequenas Missionárias de Maria Imaculada - Hospital Madre Teresa
City
Belo Horizonte
ZIP/Postal Code
30441-070
Country
Brazil
Facility Name
Fundacao para o Desenvolvimento Medico Hospitalar (UNESP Botucatu)
City
Botucatu
ZIP/Postal Code
18618-686
Country
Brazil
Facility Name
Secretaria da Saude do Estado do Ceara - Hospital Doutor Carlos Alberto Studart Gomes
City
Fortaleza
ZIP/Postal Code
60840-285
Country
Brazil
Facility Name
Universidade Federal de Goias - Hospital das Clinicas da UFG
City
Goiânia
ZIP/Postal Code
74605-020
Country
Brazil
Facility Name
Hospital das Clinicas de Porto Alegre
City
Porto Alegre
ZIP/Postal Code
90035-007
Country
Brazil
Facility Name
Irmandade Santa Casa de Misericordia de Porto Alegre
City
Porto Alegre
ZIP/Postal Code
90035-074
Country
Brazil
Facility Name
União Brasileira de Educação e Assistência-Hospital São Lucas da PUCRS
City
Porto Alegre
ZIP/Postal Code
90610-000
Country
Brazil
Facility Name
Hospital Das Clinicas Da Faculdade De Medicina Da USP
City
Sao Paulo
ZIP/Postal Code
05403-000
Country
Brazil
Facility Name
SPDM - Associacao Paulista para o Desenvolvimento da Medicina - Hospital Sao Paulo
City
São Paulo
ZIP/Postal Code
04024-002
Country
Brazil
Facility Name
National Heart Hospital
City
Sofia
ZIP/Postal Code
1309
Country
Bulgaria
Facility Name
University Multiprofile Hospital for Active Treatment- UMHAT Sveta Anna AD
City
Sofia
ZIP/Postal Code
1750
Country
Bulgaria
Facility Name
Alberta Health Services
City
Calgary
State/Province
Alberta
ZIP/Postal Code
T1Y 6J4
Country
Canada
Facility Name
University of Alberta
City
Edmonton
State/Province
Alberta
ZIP/Postal Code
T6G 2G3
Country
Canada
Facility Name
Vancouver General Hospital
City
Vancouver
State/Province
British Columbia
ZIP/Postal Code
V5Z 1M9
Country
Canada
Facility Name
London Health Sciences Centre
City
London
State/Province
Ontario
ZIP/Postal Code
N6A 5W9
Country
Canada
Facility Name
Beijing Anzhen Hospital
City
Beijing
ZIP/Postal Code
100029
Country
China
Facility Name
The Second Xiangya Hospital of Central South Hospital
City
Changsha
ZIP/Postal Code
410011
Country
China
Facility Name
The First Affiliated Hospital of Guangzhou Medical University
City
Guangzhou
ZIP/Postal Code
510120
Country
China
Facility Name
Jiangsu Province Hospital
City
Nanjing
Country
China
Facility Name
Shanghai Pulmonary Hospital
City
Shanghai
ZIP/Postal Code
200433
Country
China
Facility Name
The General Hospital of Northern Theater Command
City
Shenyang
ZIP/Postal Code
110000
Country
China
Facility Name
Tianjin Medical University General Hospital
City
Tian Jin
ZIP/Postal Code
300052
Country
China
Facility Name
The First Affiliated Hospital of Xi'an Jiaotong University
City
Xi'An
ZIP/Postal Code
710061
Country
China
Facility Name
General University Hospital II.department of Internal Medicine-cardiology and angiology
City
Praha 2
ZIP/Postal Code
128 08
Country
Czechia
Facility Name
Universitatsklinikum Bonn
City
Bonn
ZIP/Postal Code
53105
Country
Germany
Facility Name
Universitätsklinikum Carl Gustav Carus Dresden
City
Dresden
ZIP/Postal Code
01307
Country
Germany
Facility Name
Universitaetsklinikum Giessen
City
Giessen
ZIP/Postal Code
35392
Country
Germany
Facility Name
Universitat Greifswald
City
Greifswald
ZIP/Postal Code
17475
Country
Germany
Facility Name
Universitaetsklinikum Hamburg Eppendorf
City
Hamburg
ZIP/Postal Code
20246
Country
Germany
Facility Name
Thoraxklinik am Universitätsklinikum Heidelberg
City
Heidelberg
ZIP/Postal Code
69126
Country
Germany
Facility Name
Kardiologische Praxis Papenburg
City
Papenburg
ZIP/Postal Code
26871
Country
Germany
Facility Name
Universitaetsklinikum Regensburg
City
Regensburg
ZIP/Postal Code
93053
Country
Germany
Facility Name
Klinikum Würzburg Mitte gGmbH Standort Missioklinik
City
Würzburg
ZIP/Postal Code
97074
Country
Germany
Facility Name
Semmelweis Egyetem,Pulmonológiai Klinika
City
Budapest
ZIP/Postal Code
1083
Country
Hungary
Facility Name
Gottsegen György Országos Kardiológiai Intézet, Felnőtt kardiológiai osztály
City
Budapest
ZIP/Postal Code
1096
Country
Hungary
Facility Name
Pecsi Tudomanyegyetem Klinikai Kozpont
City
Pecs
ZIP/Postal Code
7624
Country
Hungary
Facility Name
Szegedi Tudomanyegyetem
City
Szeged
ZIP/Postal Code
6725
Country
Hungary
Facility Name
Azienda Ospedaliero Universitaria Consorziale Policlinico di Bari
City
Bari
ZIP/Postal Code
70124
Country
Italy
Facility Name
Cardiologia c/o Spedali Civili
City
Brescia
ZIP/Postal Code
25123
Country
Italy
Facility Name
Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico
City
Milano
ZIP/Postal Code
20122
Country
Italy
Facility Name
Azienda Ospedaliera San Gerardo
City
Monza
ZIP/Postal Code
20090
Country
Italy
Facility Name
Ospedale San Francesco
City
Nuoro
ZIP/Postal Code
08100
Country
Italy
Facility Name
IRCCS Policlinico San Matteo, Università degli studi di Pavi
City
Pavia
ZIP/Postal Code
27100
Country
Italy
Facility Name
Policlinico Umberto I
City
Roma
ZIP/Postal Code
00161
Country
Italy
Facility Name
The University of Tokyo Hospital
City
Bunkyo
ZIP/Postal Code
113-8655
Country
Japan
Facility Name
Chiba University Hospital
City
Chiba
ZIP/Postal Code
260-8677
Country
Japan
Facility Name
Kyushu University Hospital
City
Fukuoka
ZIP/Postal Code
812-8582
Country
Japan
Facility Name
Fukushima Medical University Hospital
City
Fukushima
ZIP/Postal Code
960-1295
Country
Japan
Facility Name
Gunma University Hospital
City
Gunma
ZIP/Postal Code
371-0034
Country
Japan
Facility Name
Kure Kyosai Hospital
City
Hiroshima
ZIP/Postal Code
737-8505
Country
Japan
Facility Name
Tokai University Hospital
City
Isehara
ZIP/Postal Code
259-1193
Country
Japan
Facility Name
Kagoshima University Hospital
City
Kagoshima City
ZIP/Postal Code
890-8544
Country
Japan
Facility Name
Kanazawa University Hospital
City
Kanazawa
ZIP/Postal Code
920-8641
Country
Japan
Facility Name
Kobe University Hospital
City
Kobe
ZIP/Postal Code
650-0017
Country
Japan
Facility Name
Kumamoto University Hospital
City
Kumamoto-City
ZIP/Postal Code
860-8556
Country
Japan
Facility Name
Kurume University Hospital
City
Kurume
ZIP/Postal Code
830-0011
Country
Japan
Facility Name
University Hospital Kyoto Perfectural University of Medicine
City
Kyoto
ZIP/Postal Code
602-8566
Country
Japan
Facility Name
Kyoto University Hospital
City
Kyoto
ZIP/Postal Code
606-8507
Country
Japan
Facility Name
Shinshu University Hospital
City
Matsumoto
ZIP/Postal Code
390-8621
Country
Japan
Facility Name
Kyorin University Hospital
City
Mitaka
ZIP/Postal Code
181-8611
Country
Japan
Facility Name
Nagasaki University Hospital
City
Nagasaki-shi
ZIP/Postal Code
852-8501
Country
Japan
Facility Name
Okayama University Hospital
City
Okayama
ZIP/Postal Code
700-8558
Country
Japan
Facility Name
National Hospital Organization Okayama Medical Center
City
Okayama
ZIP/Postal Code
701-1192
Country
Japan
Facility Name
Hokkaido University Hospital
City
Sapporo-shi
ZIP/Postal Code
060-8648
Country
Japan
Facility Name
Sapporo Medical University Hospital
City
Sapporo
ZIP/Postal Code
060-8543
Country
Japan
Facility Name
Tohoku University Hospital
City
Sendai
ZIP/Postal Code
980-8574
Country
Japan
Facility Name
National Cerebral and Cardiovascular Center
City
Suita-Shi
ZIP/Postal Code
564-8565
Country
Japan
Facility Name
Juntendo University Hospital
City
Tokyo
ZIP/Postal Code
113-8431
Country
Japan
Facility Name
University of Tsukuba Hospital
City
Tsukuba-City
ZIP/Postal Code
305-8576
Country
Japan
Facility Name
Mie University Hospital
City
Tsu
ZIP/Postal Code
514-8507
Country
Japan
Facility Name
Institut Jantung Negara (National Heart Institute)
City
Kuala Lumpur
ZIP/Postal Code
50400
Country
Malaysia
Facility Name
Sarawak Heart Center
City
Kuching
ZIP/Postal Code
94300
Country
Malaysia
Facility Name
Instituto Nacional de Cardiologia Dr. Ignacio Chavez
City
Mexico
ZIP/Postal Code
14080
Country
Mexico
Facility Name
Unidad de Investigacion Clinica en Medicina S.C. (UDICEM)
City
Monterrey
ZIP/Postal Code
64718
Country
Mexico
Facility Name
Klinika Kardiologii z Oddzialem Intensywnego Nadzoru Kardiologicznego, UM w Białymstoku
City
Białystok
ZIP/Postal Code
15-276
Country
Poland
Facility Name
Szpital Uniwersytecki nr 2 im dr Jana Biziela w Bydgoszczy, Klinika Kardiologii
City
Bydgoszcz
ZIP/Postal Code
85-168
Country
Poland
Facility Name
Uniwersyteckie Centrum Kliniczne
City
Gdansk
ZIP/Postal Code
80-214
Country
Poland
Facility Name
GCM SUM, I Oddzial Kardiologii
City
Katowice
ZIP/Postal Code
40-635
Country
Poland
Facility Name
Oddzial Kardiologii Wojewodzki Szpital Specjalistyczny im. W.Bieganskiego
City
Lodz
ZIP/Postal Code
91-347
Country
Poland
Facility Name
Wojewodzki Szpital Specjalistyczny im. Stefana Kardynala Wyszynskiego SPZOZ, Oddzial Kardiologii
City
Lublin
ZIP/Postal Code
20-718
Country
Poland
Facility Name
ECZ Otwock Klinika Kardiologii, Klinika Krążenia Płucnego Chorób Zakrzepowo-Zatorowych i Kardiologii
City
Otwock
ZIP/Postal Code
05-400
Country
Poland
Facility Name
SPSK2 PUM, Klinika Kardiologii
City
Szczecin
ZIP/Postal Code
70-111
Country
Poland
Facility Name
Wojewodzki Szpital Specjalistyczny, Oddzial Kardiologiczny
City
Wrocław
ZIP/Postal Code
51-124
Country
Poland
Facility Name
Altay Regional Cardiological Dispensary
City
Barnaul
ZIP/Postal Code
656055
Country
Russian Federation
Facility Name
Scientific and Research Institution of Cardiovascular Diseases Complex Problems
City
Kemerovo
ZIP/Postal Code
650002
Country
Russian Federation
Facility Name
National Medical Research Center of Cardiology of MoH of Russian Federation
City
Moscow
ZIP/Postal Code
121552
Country
Russian Federation
Facility Name
GU Moscow Regional Research Clinical Institute n.a. M.F.Vla
City
Moscva
ZIP/Postal Code
129090
Country
Russian Federation
Facility Name
National medical Research Center n.a. V.A.Almazov of MoH of Russian Federation
City
Saint-Petersburg
ZIP/Postal Code
197341
Country
Russian Federation
Facility Name
Samara Regional Clinical Cardiological Dispensary
City
Samara
ZIP/Postal Code
443070
Country
Russian Federation
Facility Name
Abdullah, IA
City
Durban
ZIP/Postal Code
4001
Country
South Africa
Facility Name
Dr Kalla
City
Lenasia
ZIP/Postal Code
1820
Country
South Africa
Facility Name
Hosp. Clinic I Provincial de Barcelona
City
Barcelona
ZIP/Postal Code
08036
Country
Spain
Facility Name
Hosp. Univ. Vall D Hebron
City
Barcelona
ZIP/Postal Code
8035
Country
Spain
Facility Name
Hosp. Univ. Ramon Y Cajal
City
Madrid
ZIP/Postal Code
28034
Country
Spain
Facility Name
Hosp. Univ. Fund. Jimenez Diaz
City
Madrid
ZIP/Postal Code
28040
Country
Spain
Facility Name
Hosp. Univ. La Paz
City
Madrid
ZIP/Postal Code
28046
Country
Spain
Facility Name
Hosp. Clinico Univ. de Salamanca
City
Salamanca
ZIP/Postal Code
37007
Country
Spain
Facility Name
Hosp. Univ. Marques de Valdecilla
City
Santander
ZIP/Postal Code
39011
Country
Spain
Facility Name
Hosp. Virgen de La Salud
City
Toledo
ZIP/Postal Code
45004
Country
Spain
Facility Name
Hosp. Gral. Univ. Valencia
City
Valencia
ZIP/Postal Code
46014
Country
Spain
Facility Name
Kaohsiung Veterans General Hospital
City
Kaohsiung
ZIP/Postal Code
813
Country
Taiwan
Facility Name
National Cheng Kung University Hospital
City
Tainan
ZIP/Postal Code
704
Country
Taiwan
Facility Name
National Taiwan University Hospital
City
Taipei
ZIP/Postal Code
10002
Country
Taiwan
Facility Name
Mackay Memorial Hospital
City
Taipei
ZIP/Postal Code
10449
Country
Taiwan
Facility Name
Taipei Veterans General Hospital
City
Taipei
ZIP/Postal Code
112
Country
Taiwan
Facility Name
Chang-Gung Memorial Hospital, LinKou Branch
City
Taoyuan
ZIP/Postal Code
333
Country
Taiwan
Facility Name
Cukurova University Medical Faculty
City
Adana
ZIP/Postal Code
01790
Country
Turkey
Facility Name
Hacettepe University Medical Faculty
City
Ankara
ZIP/Postal Code
6100
Country
Turkey
Facility Name
Ankara University Medical Faculty
City
Ankara
ZIP/Postal Code
6500
Country
Turkey
Facility Name
Bursa Yuksek Ihtisas Training and Research Hospital
City
Bursa
ZIP/Postal Code
16310
Country
Turkey
Facility Name
Istanbul University - Cerrahpasa Cardiology Institution
City
Istanbul
ZIP/Postal Code
34096
Country
Turkey
Facility Name
Istanbul University Cerrahpasa Medical Faculty
City
Istanbul
ZIP/Postal Code
34096
Country
Turkey
Facility Name
Marmara University Medical Faculty
City
Istanbul
ZIP/Postal Code
34899
Country
Turkey
Facility Name
Ege University School of Medicine
City
Izmir
ZIP/Postal Code
35100
Country
Turkey
Facility Name
Dokuz Eylul University Hospital
City
Izmir
ZIP/Postal Code
35340
Country
Turkey
Facility Name
Kartal Kosuyolu Yuksek Ihtisas Egitim Ve Arastirma Hastanesi
City
Kartal-Istanbul
ZIP/Postal Code
34865
Country
Turkey
Facility Name
Konya Selcuk University Medical Faculty
City
Konya
ZIP/Postal Code
42131
Country
Turkey
Facility Name
Mersin University Medical Faculty
City
Mersin
ZIP/Postal Code
33110
Country
Turkey

12. IPD Sharing Statement

Plan to Share IPD
Yes
IPD Sharing Plan Description
The data sharing policy of the Janssen Pharmaceutical Companies of Johnson & Johnson is available at www.janssen.com/clinical-trials\transparency. As noted on this site, requests for access to the study data can be submitted through Yale Open Data Access (YODA) Project site at yoda.yale.edu.
IPD Sharing URL
https://www.janssen.com/clinical-trials/transparency

Learn more about this trial

Clinical Study to Compare the Efficacy and Safety of Macitentan and Tadalafil Monotherapies With the Corresponding Fixed-dose Combination Therapy in Subjects With Pulmonary Arterial Hypertension (PAH)

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